Bacteroides gingivalis is an anaerobic gram-negative rod that is associated with periodontal disease and local or systemic infections of oral origin. It is, however, not known if cellular and/or humoral immune mechanisms play a role in protection from infection. Recent studies have demonstrated a heterogeneity of virulence among different B. gingivalis isolates, with certain strains producing a localized abscess at the injection site ("non-invasive"), while others produce a lesion at a site different from the primary site ("invasive"). A better understanding of this host-bacteria relationship will aid in our understanding of the pathogenesis associated with B. gingivalis infections and whether cell-modulated and/or humoral immune mechanisms can modulate secondary spread by an invasive strain. The following specific aims are proposed. 1. To identify the B. gingivalis strains that yield maximal protection to secondary spread by an invasive isolate. Mice will be immunized with an invasive B. gingivalis strain (live or dead organisms) and challenged with live organisms of an invasive strain. These studies will help to elucidate immunization protocols that yield maximal protection. 2. To determine which antigen(s) is responsible for protection. Using the invasive B. gingivalis strain that provided maximal protection from a spreading infection, various antigen extracts will be prepared. Mice will be immunized with these antigens using protocols developed in Aim 1, then challenged with an invasive B. gingivalis strain. The antigen(s) that demonstrate protection will be characterized. 3. To determine whether protection is mediated by humoral and/or cellular immunity. Serum antibody or lymphocytes from immunized mice will be passively transferred to non-immunized recipients. These recipient mice will be challenged with an invasive B. gingivalis strain. If secondary spread is delayed or prevented by antibody we will determine if there is a correlation of serum antibody titer to the specific antigen with degree of protection. If immunity is mediated by immune cells, we will determine the role of T cell subsets and/or B cells in this protective immune response. 4. To assess the immune reactivity of antigen-specific T or B cell lines. Antigen specific T and B cell lines will be prepared from mouse and human lymphocytes and tested for their in vitro responses to bacterial antigens, as assessed by lymphoproliferative responses, IL-2 production, phenotype cell cycle analysis and cell product (e.g. suppressor factors and/or specific antibody). The cell products can be tested in the mouse model for prevention of secondary spread by an invasive B. gingivalis strain.